title: In vivo tumor targeting and image-guided drug delivery with antibody-conjugated, radiolabeled mesoporous silica nanoparticles.
abstract: Since the first use of biocompatible mesoporous silica (mSiO2) nanoparticles as drug delivery vehicles, in vivo tumor targeted imaging and enhanced anticancer drug delivery has remained a major challenge. In this work, we describe the development of functionalized mSiO2 nanoparticles for actively targeted positron emission tomography (PET) imaging and drug delivery in 4T1 murine breast tumor-bearing mice. Our structural design involves the synthesis, surface functionalization with thiol groups, PEGylation, TRC105 antibody (specific for CD105/endoglin) conjugation, and (64)Cu-labeling of uniform 80 nm sized mSiO2 nanoparticles. Systematic in vivo tumor targeting studies clearly demonstrated that (64)Cu-NOTA-mSiO2-PEG-TRC105 could accumulate prominently at the 4T1 tumor site via both the enhanced permeability and retention effect and TRC105-mediated binding to tumor vasculature CD105. As a proof-of-concept, we also demonstrated successful enhanced tumor targeted delivery of doxorubicin (DOX) in 4T1 tumor-bearing mice after intravenous injection of DOX-loaded NOTA-mSiO2-PEG-TRC105, which holds great potential for future image-guided drug delivery and targeted cancer therapy.
authors.affiliation: Department of Radiology, University of Wisconsin -Madison, Wisconsin 53706, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hector F
authors.initials: HF
authors.lastname: Valdovinos
authors.forename: Sixiang
authors.initials: S
authors.lastname: Shi
authors.forename: Glen S
authors.initials: GS
authors.lastname: Kwon
authors.forename: Charles P
authors.initials: CP
authors.lastname: Theuer
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D004337:Drug Carriers; D018796:Immunoconjugates / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D049268:Positron-Emission Tomography; D012822:Silicon Dioxide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D018796:Immunoconjugates; D012822:Silicon Dioxide